SUSCEPTIBILITY OF PLASMODIUM-FALCIPARUM TO QUININE IN-VITRO - EFFECTSOF DRUG CONCENTRATIONS AND TIME OF EXPOSURE

We have studied the relationship between quinine concentrations rangin g from 0.16 to 332 mu mol/L in a blood-medium mixture and the time of exposure (12-168 h) needed for inhibition of Plasmodium falciparum (F3 2 strain) in continuous culture. When we exposed the parasites for 12 h, only brief inhibition was observed. After 24 h of exposure, parasit es were inhibited for 2-3 d at quinine concentrations greater than or equal to 10.4 mu mol/L. With 48 and 72 h of exposure, the inhibition l asted for 6-8 d at concentrations greater than or equal to 1.3 mu mol/ L and for 8-11 d at concentrations between 2.6 and 166 mu mol/L. After 96 h of exposure, parasites were inhibited for 11-17 d at concentrati ons greater than or equal to 0.65 mu mol/L. With 168 h of exposure, pa rasites were inhibited at all quinine concentrations greater than or e qual to 0.65 mu mol/L during 28 d of post-exposure cultivation. After reappearance, parasites multiplied on average 7.6 fold during each par asite schizogony cycle. The calculated parasite elimination rate in th e presence of effective concentrations of quinine was 99.7-99.9% per c ycle. We conclude that the elimination rate of the parasites is concen tration-dependent at low concentrations of quinine in vitro. As soon a s a threshold concentration of 0.65-2.6 mu mol/L is attained, only the exposure time determines parasite elimination. These experiments sugg est that it might be preferable to reduce each dose rather than the du ration of treatment in areas where P. falciparum is susceptible to qui nine.